Rubella

Rubella
Last updated: October 15, 2018

Vaccine-Preventable Diseases 1
WHO Vaccine-Preventable Diseases Surveillance Standards
Surveillance Standards
 Rubella

DISEASE AND VACCINE CHARACTERISTICS

Rubella is an acute viral disease traditionally affecting
susceptible children and young adults. Its public health
importance is due mainly to the teratogenic potential
of the virus, causing harm to an embryo or fetus. The
incubation period of rubella is 14 days, with a range of
12–23 days. Apart from the congenital infection, rubella
is a mild self-limiting illness that usually occurs during
childhood. During the second week after exposure,
there may be a prodromal illness consisting of fever,
malaise and mild conjunctivitis. Prodromal symptoms
are more common in adults than children. Postauricular,
occipital and posterior cervical lymphadenopathy is
characteristic, and typically precedes the rash by 5–10
days. The maculopapular, erythematous and often
pruritic rash occurs in 50–80% of rubella-infected
persons. The rash, usually lasting one to three days,
starts on the face and neck before progressing down the
body. Joint symptoms (arthritis, arthralgias), usually of
short duration, may occur in up to 70% of adult women
with rubella but are less common in men and children.
Post-infectious encephalitis occurs in approximately
1/6000 rubella cases, but occasionally incidences have
been reported as high as 1/500 and 1/1600 (1). Rubella
infection occurring just before conception and during
early pregnancy often results in miscarriage, fetal or
early infant death, or multi-organ congenital defects
known as congenital rubella syndrome (CRS). CRS
risk is unrelated to severity of symptoms in the mother.
Surveillance for CRS is discussed in a different chapter.
Rubella-containing vaccines (RCV) are live attenuated
virus vaccines, most often combined with measles
and sometimes mumps and varicella vaccines (MR,
MMR, MMRV). The vaccine has been highly effective
at reducing the burden of disease, and has led to the
elimination of rubella and CRS from several Western
Pacific and European countries as well as all countries
in the Americas. As of 2017, three WHO regions have
rubella elimination goals (2).

FIGURE Timeline of infectivity, clinical disease and laboratory findings

1 for rubella virus infection

RASH ONSET

DAYS -23 ... -12 -11 -10 -9 -8 -7 -6 -5 -4 -3 -2 -1 0 1 2 3 4 5 6 7 8 9 10 11 12 ... 23 24 25 26 27 28 29 30

INFECTIVITY

Exposure
period

Infectious period

prodrome
1-5 days
CLINICAL

lymphadenopathy

rash
1-3 days
LAB SPECIMEN/

Adequate sample collection for IgM testing

DIAGNOSTICS

IgM (optimal sensitivity)

PCR (max viral shedding)

Horizontal bars represent range of possible days, with day 0 as the day of rash onset. For lab specimen/diagnostics,
bars represent the range of days in which that particular test would be positive.

3
WHO Vaccine-Preventable Diseases Surveillance Standards
 RATIONALE AND OBJECTIVES OF SURVEILLANCE

GLOBAL OR REGIONAL LEVEL

The key global objective of rubella surveillance is to BOX Integration of rubella and
measure progress towards elimination, and to document
elimination, in five of six WHO regions by 2020. 1 measles surveillance

NATIONAL OR LOCAL LEVEL

The objectives of rubella surveillance at these levels
Integrate rubella and measles
are to:
surveillance, whenever possible.
Both diseases present similarly
hh detect and confirm cases to document the burden of clinically with a rash illness, and
rubella in countries that have not introduced RCV both have regional targets for
hh detect and confirm cases to monitor the impact elimination. As such, both have
of the vaccination programme, and implement similar approaches to surveillance.
additional vaccination strategies as appropriate Laboratory test suspected cases
of measles and rubella either in
hh detect and confirm rubella infection in pregnant parallel or in series, depending
women, facilitate proper referrals and document the
on local epidemiology and public
pregnancy outcome
health priorities. This chapter
hh investigate cases to determine the source and factors specifically addresses rubella
related to transmission surveillance, although many details
would also pertain to measles
hh identify high-risk populations and areas
surveillance. See the Measles
hh verify the absence of endemic rubella cases to chapter for additional information
document achievements of national targets, such as about measles.
elimination of endemic virus

hh model the expected CRS incidence in a population

based on rubella incidence.

hh identify babies with CRS to ensure proper infection

control measures are implemented to prevent further
spread of infection

BOX
How CRS surveillance relates to rubella surveillance
2
CRS surveillance systems are separate from clinical rubella surveillance, and so are
addressed in a different chapter in these surveillance standards. The surveillance
systems for the two manifestations of rubella infection (acquired or congenital)
differ substantially in terms of case definitions, age groups of interest and sites for
case detection. The two surveillance systems are linked when a pregnant woman
is identified who has acquired rubella infection and the pregnancy outcome is
followed, including an assessment to see if the newborn has CRS. Despite having
distinct methodology and approaches, the results of the two surveillance systems
often need to be interpreted together, as both are manifestations of the same
viral infection and are linked in terms of public health significance and implications
for vaccination.

4
Rubella

TYPES OF SURVEILLANCE RECOMMENDED
MINIMAL SURVEILLANCE
Because rubella surveillance should be integrated
with measles, and all countries should be conducting
elimination-standard surveillance for measles, WHO
recommends elimination-standard surveillance for
rubella simultaneously. Rubella surveillance should be
case-based. Surveillance should be a system that can, in
a timely manner, detect, notify and investigate suspected
cases and outbreaks, correctly classify them as confirmed
or discarded, and inform actions that reduce morbidity
and mortality and prevent further virus transmission
(2). Surveillance should be national with inclusion of all
CASE DEFINITIONS AND FINAL CLASSIFICATION
SUSPECTED CASE DEFINITION FOR CASE FINDING
A suspected rubella case is a patient with fever and
maculopapular (non-vesicular) rash, or in whom a
healthcare worker suspects rubella. A healthcare worker
should suspect rubella when a patient presents with
the following: fever, maculopapular rash and cervical,
suboccipital or postauricular adenopathy or arthralgia/
arthritis.
FINAL CASE CLASSIFICATION (FIGURE 2)
hh Laboratory-confirmed rubella case: A suspected case
of rubella that has been confirmed positive by testing
in a proficient laboratory. A proficient laboratory
is one that is WHO accredited or has established
a recognized quality assurance programme, such as
International Organization for Standards (ISO) or
Clinical Laboratory Improvement Amendments
(CLIA) certification (3).
hh Epidemiologically linked rubella case: A suspected
case of rubella that has not been confirmed by a
laboratory, but was geographically and temporally
related, with dates of rash onset occurring 12–23
days apart from a laboratory-confirmed case or
another epidemiologically linked rubella case.
hh Clinically compatible case: A suspected case with
maculopapular (non-vesicular) rash and fever (if
measured) and at least one of arthritis/arthralgia
or lymphadenopathy, but no adequate clinical
WHO Vaccine-Preventable Diseases Surveillance Standards
Rubella
health facilities (both private and public), with a system
for zero reporting (reporting that there were no cases).
Countries may initially identify rubella cases through
testing of sera that were negative for measles.
LINKAGES TO OTHER SURVEILLANCE
Surveillance for rubella should be done together with
measles, as mentioned previously. Additionally, given the
broad suspected case detection definition discussed below,
other rash-causing diseases, like dengue, can be integrated
into this surveillance system.
specimen was taken and the case has not been
linked epidemiologically to a laboratory-confirmed
case of rubella or other communicable disease.
In a low incidence setting, the vast majority of
rubella cases should be confirmed by laboratory or
epidemiological linkage. Clinically compatible cases
are highly unlikely to be rubella when the country is
at or near elimination.
hh Non-rubella discarded case: A suspected case that
has been investigated and discarded as a non-rubella
(and non-measles) when any of the following are
true:
»» negative laboratory testing in a proficient
laboratory on an adequate specimen collected
during the proper time period after rash onset
(see Figure 1)
»» epidemiological linkage to a laboratory-
confirmed outbreak of another communicable
disease that is not rubella
»» confirmation of another etiology, regardless
of whether it meets the definition of
epidemiological linkage
»» failure to meet the clinically compatible rubella
case definition.
If the case is also negative for measles, this is a non-
measles non-rubella discarded case.
5
 FIGURE
Classification of suspected measles and rubella cases
2

MEASLES:
LABORATORY-
LABORATORY
CONFIRMED
POSITIVE
MEASLES

RUBELLA: LABORATORY-
ADEQUATE
LABORATORY CONFIRMED
SPECIMEN POSITIVE RUBELLA

MEASLES/ DISCARDED:
RUBELLA: NON-
LABORATORY MEASLES,
NEGATIVE NON-RUBELLA

EPIDEMIOLOGICALLY LINKED EPIDEMIO-

TO LABORATORY-CONFIRMED OR LOGICALLY
SUSPECTED ANOTHER EPIDEMIOLOGICALLY LINKED
CASE LINKED MEASLES CASE MEASLES

EPIDEMIOLOGICALLY LINKED EPIDEMIO-

TO LABORATORY-CONFIRMED OR LOGICALLY
ANOTHER EPIDEMIOLOGICALLY LINKED
LINKED RUBELLA CASE RUBELLA

NO OR
INADEQUATE
EPIDEMIO-
SPECIMEN DISCARDED:
LOGICALLY
NON-
LINKED TO A
MEASLES,
DIFFERENT
NON-RUBELLA
DISEASE

DOES NOT MEET

DISCARDED:
CLINICAL
NON-
CASE
NO MEASLES,
DEFINITION
EPIDEMIO- NON-
FOR MEASLES
LOGICAL RUBELLA
OR RUBELLA
LINKAGE
TO MEASLES
OR RUBELLA MEETS
CONFIRMED CLINICAL CLINICALLY
CASE CASE COMPATIBLE
DEFINITION MEASLES
FOR MEASLES

MEETS
CLINICAL CLINICALLY
CASE COMPATIBLE
DEFINITION RUBELLA
FOR RUBELLA

6
Rubella

OTHER DEFINITIONS
hh Endemic rubella case: Confirmed cases of rubella
resulting from endemic transmission of rubella.
Endemic transmission is defined as a chain of rubella
virus transmission that is continuous for ≥ 12 months
within a country. To the greatest extent possible,
this chain of transmission should be defined based
on genotyping evidence along with epidemiological
investigation. It is often the case that chains of
transmission are unclear for rubella because of the
mild presentation of many cases.
hh Imported rubella case: A returning traveler or visitor
exposed to rubella outside the country during all
or part of the 12–23 days prior to rash onset and
supported by epidemiological or virological evidence.
For cases that were outside the country for only a
part of the 12–23 day interval prior to rash onset,
conduct additional investigation of whether the
exposure to another rubella case likely occurred
outside or within the country to determine the
source of infection and whether the case can be
CASE INVESTIGATION
All suspected rubella cases should be notified within
24 hours of identification and investigated within
48 hours of notification. A case investigation should
be conducted on each case, with data collected on
potential risks of exposure and spread among contacts
to identify transmission patterns and interrupt chains
of transmission. The source of infection for rubella is an
infectious person who interacted with the case 12–23
days before rash onset.
Once the case investigation form has been completed
and laboratory test results are available, suspected
cases should be classified both by confirmation status
(laboratory-confirmed, epidemiologically linked,
clinically compatible, discarded) and by source of
infection (imported, importation-related, endemic,
unknown). As few cases as possible should be classified
as clinically compatible because there are many other
causes of rash that may mimic rubella infection. An
WHO Vaccine-Preventable Diseases Surveillance Standards
Rubella
considered imported. Imported cases are defined
by the place where the case was infected, not the
country of residence or origin of the case. When
possible, add genotyping evidence, particularly new
subtyping methods, to epidemiological investigation
in order to better define the chain of transmission.
hh Importation-related rubella case: A locally
acquired infection that occurs as part of a chain of
transmission originating from an imported case as
supported by epidemiological or virological evidence.
If transmission of rubella from cases related to
importation persists for 12 months or more within a
country, cases are no longer considered importation-
related but endemic.
hh Unknown source rubella case: A confirmed case
for which no epidemiological or virological link
to importation or endemic transmission can be
established after a thorough investigation.
important difference from measles is that the source of
a rubella case can be difficult to identify because of the
mild presentation of rubella. A significant proportion
of rubella cases are subclinical, so a more extensive
investigation is needed to minimize the number
of transmission chains with an unknown source of
infection.
The investigation of suspected cases who are pregnant
woman (or the evaluation of contacts who are pregnant)
will vary by country. However, follow up of pregnant cases
and pregnant contacts until the end of the pregnancy
to determine the outcome of the pregnancy, including
assessment of the newborn for CRS. For all laboratory-
confirmed cases of rubella infection during pregnancy, the
patient’s name and other relevant information should be
entered into a rubella pregnancy register. Counselling and
medical follow-up must be assured.
7
 SPECIMEN COLLECTION
Collect specimens on every suspected case because the
symptoms of rubella are non-specific. Several different
types of specimens can be collected from suspected
rubella cases based on the timing of investigation (Table
1) (3). Collect specimens on first contact with the case;
do not wait for the ideal window or the case might be
lost to follow up. An adequate specimen for antibody
detection is defined as a sample collected within 28 days
after rash onset that consists of ≥ 0.5mL of sera; the
volume of whole blood to be collected is based on age. In
some regions where suitable testing is available, you may
also use a sample of oral fluid or dried blood on a filter
paper (≥ 3 fully filled circles).
At a minimum, all cases should have a sample
collected for antibody detection (unless they can be
epidemiologically linked to a laboratory-confirmed or
another epidemiologically linked case). If the case is not
part of a known chain of transmission, collect a sample
for viral isolation (genotyping) from 5–10 cases early
in the chain of transmission and every two months
thereafter if transmission continues. Use laboratory
testing and epidemiologic linkage for case confirmation
together in a sustainable way that allows maximization
of laboratory resources. Particularly in endemic settings,
epidemiologic linkage should be prioritized during case
investigations for routine case confirmation, during
confirmed outbreaks, and in times and places where
sample collection or transportation is extremely difficult,
such as during disasters and remote locations.
In countries that are close to elimination or have been
verified, make an attempt to collect from each case a
serum specimen and a viral isolation specimen (throat,
nasal, or nasopharyngeal swab; oral fluid, urine, or
nasopharyngeal aspirates) at the correct time.
The specimens collected for rubella testing are the same
as for measles testing, primarily serum specimens for
serological testing; naso-/oro-pharyngeal or throat swab;
and oral fluid, urine or nasopharyngeal aspirates for virus
detection and isolation.
8
Specimen collection considerations for rubella vary from
that for measles in the following ways.
hh The follow-up serum sample for IgM testing should
be collected after day five post rash onset for rubella
IgM re-testing (versus after day three for measles).
Samples should still be collected on first contact with
the case.
hh Urine samples have been used successfully for both
measles and rubella virus detection and isolation,
but urine is considered to be a less sensitive sample
compared to throat swabs for rubella.
hh From patients with suspected rubella encephalitis,
cerebrospinal fluid (CSF) samples can be collected
for testing.
STORAGE AND TRANSPORT
Transport and storage requirements for rubella are
identical to the requirements for measles specimens.
hh Whole blood/serum. Collection of whole blood is
done by venipuncture using a sterile, plain collection
tube or gel separator tube without additives. Whole
blood can be stored at 4−8°C (never freeze whole
blood) for up to 24 hours or for 6 hours at 20–25°C
before the serum is separated from the clotted blood
through centrifugation. After this time, whole blood
must be transported to a facility equipped to separate
the serum in order to avoid haemolysis.
Serum should be stored at 4−8°C until shipment,
but ideally should not be held at 4-8°C for longer
than seven days. For longer periods, such as when
a delay is anticipated in shipping or testing, serum
samples must be frozen at –20°C or below and
transported to the testing laboratory on frozen ice
packs in a sufficiently insulated container. Avoid
cycles of repeated freezing and thawing, as this can
have detrimental effects on the integrity of IgM
antibodies. Aliquots of important serum specimens
should be prepared prior to freezing. As a general
Rubella
 Rubella

rule, serum specimens should be shipped to the The throat swab is collected by swabbing the
laboratory as soon as possible, and shipment should posterior pharynx, avoiding the tongue. The NP
not be delayed for the collection of additional swab has a flexible shaft. Tilt the patient’s head back
specimens. and insert the swab into the nostril parallel to the
palate. The swab should contact the mucosal surface.
Blood can be dried onto filter paper (dried blood
Place the sample in sterile tubes containing 2–3
spots, or DBS) if venipuncture is not possible, or if
mL of viral transport media (VTM) or phosphate-
a cold chain or economical method to ship serum
buffered saline (PBS). It is important to prevent the
samples are not available. While venous blood can be
swabs from drying out. The throat and NP swabs
collected for DBS, normally DBS are prepared using
may be refrigerated at 2–8°C for up to 48 hours and
capillary blood. Collect blood by finger or heel-
shipped on ice/frozen ice packs. If arrangements
prick using a sterile lancet, preferably a single-use
cannot be made for shipment within this timeframe,
disposable lancet. Allow blood specimens that have
it is best to preserve the sample at -70°C. After
been spotted on filter paper to air dry completely.
freezing at -70°C, the samples are shipped on dry
Wrap individual cards in wax paper and place them
ice. Avoid freeze/thaw cycles. If storage at -70°C is
in a sealable plastic bag with a desiccant pack. DBS
not available, store samples at -20°C; viral viability
should be stored at 4°C until they can be shopped
will be lost, but the integrity of the viral RNA may
to the laboratory. It is acceptable to transport DBS
be maintained and detected by reverse transcription-
at ambient temperatures up to 42°C if the sample is
polymerase chain reaction (RT-PCR).
delivered to the laboratory within three days.
hh Urine. Urine is collected in a suitable sterile,
hh Oral fluid (OF). An adequate OF sample is one
leak-proof container. The urine sample should be
that is collected by gently rubbing along the base of
stored at 4–8°C until the urine can be centrifuged.
the teeth and gums for at least one minute, which
Do not freeze the original urine sample prior to
should allow the sponge to absorb about 0.5 mL of
centrifugation. Whole urine samples may be shipped
crevicular fluid. If the daily ambient temperature is
in sealed containers at 4°C, but centrifugation
below 22°C, OF samples should be shipped to the
within 24 hours of collection is recommended. The
laboratory within 24 hours. At higher temperatures,
urine is centrifuged at 500 × g (approximately 1 500
the OF samples should be kept at 4–8°C until
rpm) for 5–10 minutes, preferably at 4°C and with
the samples can be shipped to the laboratory on
the supernatant removed. Add sterile VTM, tissue
cold packs. The OF samples are not considered
culture medium or PBS to the sediment to bring
a biohazard and can be shipped without special
the final volume to 2 mL. If a pellet is not visible,
documentation from the site of collection to the
remove all but 1 mL at the bottom of the centrifuge
laboratory.
tube and mix with equal volume of VTM. Store the
hh Nasopharyngeal (NP), nasal or oropharyngeal processed urine sample at 4°C and ship within 48
(OP) swabs. An oropharyngeal (throat) swab is hours. Alternatively, the urine sample may be frozen
the recommended sample for both viral detection at -70°C in viral transport medium and shipped on
and virus isolation for suspected cases. NP swabs dry ice. If storage at -70°C is not available, samples
will serve as good samples for both virus isolation can be stored at -20°C; viral viability will be lost, but
and detection but are more difficult to collect. NP the integrity of the viral RNA may be maintained
aspirates and nasal swabs are variations that have and detected by RT-PCR.
been used successfully to detect rubella virus. Swabs
Regardless of specimen type collected, all specimens
should be collected using only synthetic fiber swabs
should arrive to the lab within five days of collection,
with plastic shafts. Do not use calcium alginate
except in the case of oral fluids as noted above.
swabs or swabs with wooden shafts as they may
contain substances that inactivate viruses or inhibit
polymerase chain reaction (PCR) testing.

9
WHO Vaccine-Preventable Diseases Surveillance Standards
 TABLE
Specimen types for diagnosis of rubella (and measles)
1
TYPE OF SPECIMEN TYPE OF TEST VOLUME TO BE COLLECTED TIMING OF COLLECTION

Antibody detection* Volume of 4–7 mL of blood for ≤ 28 days after rash onset.
(rubella specific IgM, paired older children and adults; 1 mL Paired sera are normally
sera to document IgG for younger children; 0.5mL collected 10–20 days apart.
seroconversion or significant from infants The interval between the two
WHOLE BLOOD/ rise in IgG between acute and serum samples can be shorter
SERUM (BY convalescent phase sera) if virus-specific IgG was not
VENIPUNCTURE) detected in the first serum
sample.

Antibody detection* (rubella At least 3 fully filled circles on ≤ 28 days after rash onset
specific IgM, paired sera to a filter-paper collection device
document IgG seroconversion
ALTERNATIVE or significant rise in IgG)
SPECIMEN:
Detection of viral RNA by RT-
PCR
DRIED BLOOD SPOTS
(DBS) (WHOLE
BLOOD)

THROAT Viral isolation by cell culture Swab or NP aspirate Ideally, the sample should be
(RECOMMENDED), Detection of viral RNA by RT collected within 5 days, but
NASAL, OR PCR*** can collected up until 14 days
NASOPHARYNGEAL after onset of rash for virus
(NP) SWABS OR detection.
NASOPHARYNGEAL
ASPIRATES**

Antibody detection* (rubella Using a sponge collection Ideally, the sample should be
specific IgM) device that is rubbed along collected within 5 days, but
Detection of viral RNA by the gums for > 1 minute to can collected up until 14 days
RT-PCR ensure the device is thoroughly after onset of rash for virus
wet (~0.5 mL crevicular fluid). detection.
Up to 28 days if antibody
ORAL FLUID (OF) testing.

Viral isolation by cell culture Minimum 10 mL (preference Ideally, the sample should be
Detection of viral RNA by first morning void). Larger collected within 5 days, but
URINE RT-PCR volumes have a higher chance can collected up until 14 days
of detection. after onset of rash for virus
detection.

* Antibody detection. Adequate samples are those collected within 28
days after onset of rash. However, IgM detection by EIA for rubella
is more sensitive when collected 6–28 days after the onset of rash. A
second serum sample may be required for additional testing under the
following circumstances:
• Detection of virus-specific RNA by RT-PCR is either unavailable
or the results were inconclusive
• The first serum specimen was collected ≤ 3 days after rash onset and
is negative for measles IgM, or is negative in serum collected ≤ 5
days for rubella IgM by EIA
• Repeat testing of the initial serum specimen fails to resolve an
equivocal result for IgM.

10
Rubella
 Rubella

TABLE 1 CONTINUATION: SPECIMEN TYPES FOR DIAGNOSIS OF RUBELLA (AND MEASLES)

STORAGE CONDITIONS ADVANTAGES DISADVANTAGES COMMENTS

Whole blood: 4–8°C (never »»Most widely »»Sensitivity of the test is lower Laboratories should report
freeze whole blood) for collected and tested, ≤ 3 days after rash onset* results for IgM within 4 days
up to 24 hours or for 6 technically simple and »»Positive predictive value of IgM of receipt of the specimens.
hours at 20–25°C before standardized in elimination settings is low
the serum is separated »»WHO correlate of
from clotted blood protection exists
through centrifugation.
Serum should be stored
4–8°C until shipment to
laboratory, ideally no longer
than 7 days.

Does not require cold chain.
Should be dried before
storage at low humidity.
»»Does not require cold
chain
»»Potentially lower
transportation cost
»»Can collect from finger
or heel prick
»»Potential for viral RNA
isolation and antibody
detection from same
sample
»»Sensitivity reduced if not dried/ Preference is for serum to be
stored properly collected, with DBS reserved
»»Increased workload in for situations where it’s hard
laboratory to collect venous blood (e.g.
infants), reverse cold chain
»»No quality control on extraction
cannot be maintained, or
process
where expedited shipping is
»»Insufficient blood collected in not possible.
field
»»Lower sensitivity for
RT-PCR

4–8°C »»Superior to oral fluid for
virus isolation
»»Can be more sensitive
for confirmation than
serum within first 3 days
»»Requires cold chain
»»Should get to lab within 48
hours ideally
Both NP and OF samples
can be stabilized on FTA®
cards for transport at
ambient temperature. In this
case, detection of antibodies
is not possible, but viral RNA
can be detected by RT-PCR.

Does not require cold
chain if < 22°C ambient
temperature and shipped
to the laboratory within
24 hours. At higher
temperatures, the OF
samples should be kept at
4–8°C until the samples
can be shipped on cold
packs.
»»Less invasive than blood
collection
»»Does not require cold
chain
»»Potentially lower
transportation cost
»»Viral detection and
antibody detection from
same sample
»»Somewhat less sensitive for Both NP and OF samples
antibody detection than serum can be stabilized on FTA®
when collected early cards for transport at
»»Not suitable for virus isolation ambient temperature. In this
(cell culture) case, detection of antibodies
is not possible, but viral RNA
»»External quality control
can be detected by RT-PCR
programmes have not been
established
»»Limited number of EIA test kits
validated for OF
»»If stored at room temperature,
need to ship samples to lab
within 24 hours of collection

Stored at 4–8°C until the »»Often difficult to collect,

urine can be centrifuged. transport and process
Original urine sample »»Less sensitive than throat swabs
should not be frozen prior »»May contain substances that
to centrifugation. are inhibitory for RT-PCR

** Properly collected serum tested for IgM is still considered by some labs
as the only adequate specimen to rule out rubella. A negative RT-PCR
from the upper respiratory tract is not considered to rule out rubella
because specimen timing and quality are critical. However, some
countries are collecting only upper respiratory tract specimens from
infants because of the difficulty of drawing blood. In some countries
with very low rubella prevalence, these samples can be a significant
fraction of the total.
WHO Vaccine-Preventable Diseases Surveillance Standards
***Virus detection (by cell culture or RT-PCR). Because virus is
more likely to be isolated (and RNA detection rate is higher) when
specimens are collected early, the collection of specimens for virus
detection should not be delayed until laboratory confirmation by
antibody detection of a suspected case is obtained. Samples for
antibody and viral detection should be collected at first contact with
a suspected case.
11
 LABORATORY TESTING
CONFIRMATION METHODS
Laboratory case confirmation for rubella can yield the
following testing results:
hh detection of anti-rubella IgM by enzyme
immunoassay (EIA). This is the gold-standard.
Results of IgM should be reported within four
days of the specimen’s arrival to the laboratory
(Figures 3b/3c).
hh a diagnostically significant titer change in IgG
antibody level in acute or convalescent sera, or
documented seroconversion (IgG negative to IgG
positive)
hh positive RT-PCR or viral isolation in cell culture
(Figure 3a).
GENOTYPE TESTING
Rubella genotype testing can help to identify the
chain of transmission to which the case belongs. It is
recommended that at least 80% of laboratory-confirmed
chains of transmission have their genotype determined.
Molecular typing is recommended because it can provide
useful information to track the epidemiology of rubella
in a country that has eliminated rubella, and provides
monitoring data on rubella virus transmission globally.
By comparing virus sequences obtained from new
case-patients with other virus sequences, the origin of
particular virus types can be tracked.
Results from genotyping samples should be reported
within two months of the specimen’s arrival to the
laboratory.
SPECIAL LABORATORY CONSIDERATIONS
hh Sera should be collected as early as possible after
onset of illness. However, rubella-specific IgM may
be undetectable by EIA in up to 50% of rubella
cases with serum samples collected on the day of
rash onset, and a proportion of cases will be negative
if collected ≤ 5 days after rash onset. For a rubella
IgM-negative result in specimens taken on or before
five days after rash onset, repeat serologic testing on
a specimen collected after five days after rash onset.
This is extremely important to confirm cases who
are pregnant and in countries that have eliminated
rubella.
hh Upon vaccination, particularly of adults, IgM
12
antibodies may persist as long as six months after
the date of vaccination. Care should be taken when
interpreting an IgM positive result in those who have
been recently vaccinated (4).
hh False-positive serum rubella IgM tests may occur
due to the presence of rheumatoid factors (indicating
rheumatologic disease), cross-reacting IgM or
infection with other viruses (5).
hh IgG peaks between three to five weeks after rash
onset, so timing of paired sera is very important to
document seroconversion. IgG is most valuable in
a suspected case who does not have any exposures
or vaccination after the onset date and no maternal
antibody (at about nine months). IgG positivity is
then confirmatory.
hh RT-PCR negative samples should not be used to
discard a suspected case.
hh Avidity testing and detection of wild-type rubella
virus can be used to resolve uncertainties in the
serologic evaluation of suspected cases. Low avidity
is associated with recent primary rubella infection;
high avidity is associated with past infection,
vaccination, or reinfection.
hh Laboratory testing for measles. Laboratories can
perform testing on samples of suspected measles
or rubella cases using different testing algorithms,
depending on the local epidemiology and available
resources. When possible, it is best to integrate
the testing of measles and rubella. If resources
are sufficient or both diseases occur at a similar
prevalence, do measles and rubella testing in parallel,
with all samples being tested simultaneously for both
diseases. If resources are limited or measles burden
is high, do serial testing in which measles testing is
done first, followed by rubella testing on samples that
are negative for measles. If rubella burden is higher
than measles, do the rubella testing first followed
by measles testing on samples that test negative for
rubella.
hh Laboratory testing for other febrile rash illnesses.
In countries that use the fever-rash case definition
and have a high burden of other fever-rash diseases
(such as dengue, Zika and Chikungunya), additional
testing can be integrated into the measles-rubella
testing algorithm. Weigh the burden of disease and
Rubella
 Rubella

the risk of delayed diagnosis when determining the
proper algorithm.
hh Laboratory networks. WHO coordinates the
hh Laboratory testing in an elimination setting. In an
elimination setting, critically evaluate both positive
and negative IgM testing results. False positives
become more likely as the positive predictive value
of IgM testing decreases as rubella prevalence
decreases. Epidemiological data can strengthen
the argument for or against an IgM-positive result
representing a true case. A second sample may need
to be collected if the original sample that tested
negative for rubella was collected ≤ 5 days after rash
onset, to ensure they are truly negative. Figures 3a,
3b and 3c demonstrate the process for laboratory
testing for suspected measles and rubella cases when
a country is near or at elimination. Suspected cases
in low incidence settings should be evaluated and
classified after taking into consideration all laboratory
and epidemiological data.
Global Measles and Rubella Laboratory Network
(GMRLN), which is a network of over 700 labs
at national and subnational laboratories that meet
rigorous standards to provide accurate results (6).
Regional and global reference laboratories can
provide specialized testing (such as affinity testing)
and viral isolation with molecular techniques to
those countries that are unable to do this in their
own laboratories. Ensure that samples are tested in
a WHO accredited or proficient laboratory, or in
laboratories with quality assurance support from
national labs in GMRLN. If this is not possible, then
use a laboratory that has an established recognized
quality assurance programme such as ISO 15189 or
ISO 17025 accreditation, or CLIA certification.

FIGURE Laboratory testing for suspected measles or rubella cases in

3a countries at or near elimination, part I

SUSPECTED MEASLES OR RUBELLA CASE

COLLECT VIROLOGIC SPECIMEN COLLECT

(throat swab, NP swab, SPECIMEN FOR
oral fluid, urine) SEROLOGIC
TESTING
(serum or
oral fluid) FIGURE
3b
RT-PCR →

POSITIVE + NEGATIVE -

RECENT OTHER CAUSE CONFIRMED

VACCINATION? by RT-PCR in laboratories that
perform such testing routinely?

NO, YES, 7-14 DAYS YES, NO, OR TESTING

CONFIRM CASE PRIOR TO RASH DISCARD NOT PERFORMED
CASE

PERFORM SEQUENCING PERFORM

to identify and SEQUENCING
report genotype CLASSIFY BY
SEROLOGIC
TESTING
FIGURE
VACCINE WILD TYPE 3b
SEQUENCE: SEQUENCE: →
DISCARD CASE CONFIRM CASE

13
WHO Vaccine-Preventable Diseases Surveillance Standards
 FIGURE Laboratory testing for suspected measles or rubella case
in countries at or near elimination (sample collected in the
3b optimal time window), part II

SERUM OR ORAL FLUID WAS COLLECTED

≥ 4 DAYS POST RASH FOR MEASLES OR ≥ 6 DAYS FOR RUBELLA?

NO YES

TEST FOR IgM TEST FOR IgM IgM NEGATIVE1

IgM IgM POSITIVE RULE OUT

NEGATIVE OR EQUIVOCAL3 RUBELLA2 DISCARD
(RT-PCR (measles CASE
negative) IgM negative)
EPIDEMIOLOGIC LINK,
FIGURE
3c STRONG SUSPICION CONFIRM
YES
→ OR RT-PCR POSITIVE? CASE

NO

RUBELLA IgM POSITIVE MEASLES IgM POSITIVE

OR EQUIVOCAL OR EQUIVOCAL

ACUTE SERUM:
TEST FOR RUBELLA IgG

RUBELLA IgG RUBELLA IgG OTHER CAUSE CONFIRMED BY

POSITIVE + NEGATIVE - ROUTINE SEROLOGIC TESTING?

NO YES

RUBELLA AVIDITY REQUEST 2ND SERUM, DISCARD

OR 21-10 DAYS AFTER ACUTE5 CASE
TESTING IF APPROPRIATE4

»» REPEAT IgM6 SECOND SERUM UNAVAILABLE:

»» TEST FOR IgG WITH PAIRED SPECIMENS7 CONFIRM CASE

IF MEASLES REINFECTION8 IS SUSPECTED,

CONSULT WITH REGIONAL LABORATORY COORDINATOR

Notes for Figure 3b:
1 A measles reinfection case can have a negative IgM result.
If measles reinfection is suspected, consult with the regional
laboratory coordinator. Reinfection cases can be confirmed
by RT-PCR, a rise in IgG titer or by measuring high levels
of measles neutralizing antibody levels (≥ 40,000 mIU/
mL) by plaque reduction neutralization testing.
2 Parallel, or reflex, testing should be performed according
to the resources available and regional surveillance
recommendations.
3 An equivocal IgM result is obtained after repeat of test.
The equivocal or positive IgM result was obtained using a
validated assay in accredited laboratory.
14
4 A positive IgG result and an equivocal IgM for rubella
are inconsistent with primary rubella. If acute serum was
IgM positive, rubella avidity testing or evaluation of IgG
titers with paired specimens may be necessary to resolve the
case. Low avidity is associated with recent primary rubella
infection; high avidity is associated with past infection,
vaccination, or reinfection.
5 If the acute serum was IgG negative, the absence of
seroconversion can be demonstrated with a second serum
collected ≥ 10 days post rash.
6 In most instances, a suspected case with an equivocal IgM
result obtained from acute serum and a positive IgM
from the second serum confirms the case. However, an
evaluation of IgG titers may be deemed necessary to support
the IgM result.
7 Test for IgG if test is available (by semi-quantitative
EIA) using appropriately timed paired specimens,
tested together. Seroconversion or demonstration of a
diagnostically significant rise confirms the case. Absence
of seroconversion (both IgG negative) rules out the case.
Note: failure to measure a diagnostically significant rise
in titer must be interpreted with caution since the ideal
timing for demonstration of a rise in titer can vary among
individuals.
8 The rise in IgG titer from a measles reinfection case is
rapid and remarkably high titers in acute serum are typical.
Consultation with the regional laboratory coordinator
is recommended to determine if additional testing is
warranted and feasible.
Rubella
 Rubella

FIGURE Laboratory testing for suspected measles or rubella case in

3c countries at or near elimination, part III

SERUM OR ORAL FLUID, COLLECTED

≤ 3 DAYS POST RASH FOR MEASLES OR ≤ 5 DAYS FOR RUBELLA,
HAS A NEGATIVE IGM RESULT AND RT-PCR NEGATIVE (OR NO SPECIMEN)

RUBELLA YES, TEST

SUSPECTED CASE? FOR RUBELLA IgG

NEGATIVE POSITIVE RUBELLA

RUBELLA IgG - IgG DISCARD CASE1

REPORT NEGATIVE IgM RESULT;

advise that a 2nd serum (≥ 6 days)
should be collected if case remains
suspicious for M/R

2ND SERUM 2ND SERUM

OBTAINED NOT COLLECTED

CLINICALLY COMPATIBLE
TEST FOR IgM
WITH MEASLES OR RUBELLA2?

POSITIVE + NEGATIVE - NO YES

CONFIRM DISCARD DISCARD

CASE CASE CASE

FOLLOW GUIDELINES FOR

NO/INADEQUATE SPECIMEN

CASE IS CASE IS
CONFIRMED BY: DISCARDED BY:
1) Epidemiologic link 1) Epidemiologically
2) Clinically linked to other
compatible disease
2) Other confirmed
cause

Notes for Figure 3c:

1 Cases who are rubella IgM negative and rubella
IgG positive are inconsistent with acute infection.
2 Expert review as appropriate

15
WHO Vaccine-Preventable Diseases Surveillance Standards
 LABORATORY TESTING IN PREGNANT WOMEN
For pregnant women exposed to rubella, medical
management and decisions may rest on collection
and interpretation of laboratory data. Figure 4 shows
recommended laboratory testing algorithm (7).
Particular care should be taken when rubella IgM is
detected in a pregnant woman with no history of illness
or contact with a rubella-like illness. Although it is not
recommended, many pregnant women with no known
exposure to rubella are tested for rubella IgM as part
of their prenatal care. If rubella test results are IgM-
positive for persons who have no or low risk of exposure
to rubella, additional laboratory evaluation should be
conducted (see Figure 4).

FIGURE Serologic evaluation of pregnant women

4 with known exposure to rubella

IgM AND IgG AT THE TIME OF FIRST VISIT (SAVE SERA)

IgM+ / IgG+ IgM+ / IgG- IgM- / IgG- IgM- / IgG+

ACUTE INFECTION SUSCEPTIBLE IMMUNE

OR FALSE IgM POSITIVE

REPEAT IgM / IgG

COLLECT 2ND SERUM
3-4 WEEKS FROM
5-10 DAYS LATER
IgM, IgG and avidity testing SUSPECTED EXPOSURE
to be conducted (test concurrently with
first specimen)

HIGH LOW POSITIVE

AVIDITY, AVIDITY, NEGATIVE
IgM+ / IgG+
NO RISE IN RISE IN
IgG TITERS IgG TITERS
(tested together (tested together
with first serum) with first serum) REPEAT IgM / IgG
6 WEEKS IF RISK OF
EXPOSURE CONTINUES
(test concurrently with
LIKELY ACUTE first specimen)
FALSE INFECTION
POSITIVE

DISCUSS ACUTE POSITIVE

NEGATIVE
OPTIONS INFECTION IgM+ / IgG+
FOR
PREGNANCY
OUTCOME
INFECTION
DISCARDED

16
Rubella
 Rubella

DATA COLLECTION, REPORTING AND USE

Because it is recommended that measles and rubella »» Severe complications

surveillance be integrated, the case investigation forms,
• Pneumonia
databases and data reporting are usually done together
• Persistent diarrhea
for both diseases. Below is a list of general data elements
for both diseases, with rubella-specific data points • Encephalitis
indicated by *. • Thrombocytopenia*
• Other
RECOMMENDED DATA ELEMENTS
»» Hospitalizations
hh Demographic information
• History of hospitalization in 23 days prior to
»» Name (in some settings, if confidentiality is a
rash onset?
concern, the name can be omitted so long as a
• Dates of hospitalization
unique identifier exists)
• Hospitalized because of this current fever-
»» Unique identifier
rash diagnosis?
»» Place of residence (city, district, and province) »» Outcome (patient survived or died)
»» Place of infection (at least to third administrative • Date of death
level, if known)
»» For women of childbearing age
»» Date of birth (or age if date of birth not
• Number of pregnancies (including current
available)
one if pregnant)*
»» Sex • Pregnancy status*
»» Race and/or ethnicity, if appropriate in country –– Number of weeks gestation at onset of
setting illness*

»» Country of birth –– Prior evidence or date of rubella serologic

immunity, or both*
hh Reporting source
–– Number and dates of previous
»» Place of reporting (for example, county or pregnancies and location (second
district) administrative level or country) of these
»» Date of notification pregnancies*
–– Pregnancy outcome, when available
»» Date of investigation
(normal infant, termination, infant with
»» Name of clinician who suspects measles (or congenital rubella syndrome, etc.)*
rubella) hh Laboratory methods and results
hh Clinical »» Type(s) of specimen(s) collected
»» Date of rash onset »» Date of specimen(s) collection
»» Symptoms »» Date specimen(s) sent to laboratory
• Fever »» Date specimen(s) received in laboratory
• Maculopapular rash
»» Date of results from laboratory
• Cough
»» Laboratory results (serology, viral detection,
• Conjunctivitis
genotype)
• Coryza
• Lymphadenopathy*
• Arthralgia or arthritis*

17
WHO Vaccine-Preventable Diseases Surveillance Standards
 hh Vaccination status
»» Number of doses of measles-containing vaccine
• Dates of all doses of vaccine given (if card
available)
»» Number of doses of rubella-containing vaccine*
• Dates of all doses of vaccine given (if card
available)
hh Contact tracing
»» Persons who came in contact with the case 7–23
days before symptom onset (source of case’s
infection). Determine if any of them had rash
illness with fever.
»» Persons who came in contact with the case in
the seven days prior to and seven days after rash
onset (potential persons exposed by the case)
hh Epidemiological data
»» Transmission setting (infection acquired at home,
healthcare setting, daycare, school, workplace,
etc.)
»» Enrolled in a school?
• If enrolled, name of the school
»» Visited a health facility in the 7–23 days before
symptom onset?
• If yes, name of the facility
»» Travel history in the past 7–23 days?
»» Relationship to outbreak (Is the case part of an
outbreak or is it sporadic?)
hh Classification
»» Final case classification (laboratory-confirmed,
epidemiologically-linked, clinically compatible,
discarded)
»» Source (import, importation-related, unknown,
endemic)
Note: The time period of 7–23 days is used to cover both
measles and rubella exposure periods.
18
REPORTING REQUIREMENTS AND
RECOMMENDATIONS
Report and analyse case-based data on all suspected
cases, regardless of final classification, from local to
national level, to allow for adequate epidemiological
analysis. Report rubella cases regularly to the next level
of the programme within the Ministry of Health (at
least monthly, preferably weekly). Reporting should
include zero reports (reporting even when no suspected
cases have been detected during the designated reporting
time period).
Suspected cases of rubella (laboratory-confirmed,
epidemiologically linked, clinically compatible and
discarded cases) should be submitted to WHO, via
country and regional offices, at least monthly. This
includes zero reporting. Every WHO Member State
uses the Joint Reporting Form ( JRF) to report rubella
annually. Rubella is not currently reportable under
IHR (2005).
RECOMMENDED DATA ANALYSES
hh Number of suspected and confirmed cases by age,
sex, date of onset (month and year at a minimum, by
week in outbreak setting) and geographic area
hh Incidence per million population by 12-month
period and geographic area (because of seasonality, it
is not appropriate to calculate incidence for shorter
periods of time).
hh Age-specific, sex-specific and district-specific
incidence rates
hh Proportion of confirmed cases by age group and
immunization status. Suggested age groups are < 6
months, 6–8 months, 9–11 months, 1–4 years, 5–9
years, 10–14 years, 15–19 years, 20–24 years, 25–29
years, 30–44 years, ≥ 45 years, but base the age groups
on the epidemiology of the disease, vaccination
schedule and history of the vaccine programme.
hh Rubella vaccine status among confirmed and
discarded cases by year and geographic area
hh Epidemic curve showing cases over time by
genotype/named strain
Rubella

hh Proportion of cases by final classification and source
hh Maps of cases
hh Proportion of complications and death, stratified by
age
hh Number and proportion of cases in pregnant women
by trimester of exposure
hh Data summaries for endemic and imported virus
genotype and lineage characterization
Note about counting rubella cases: Total confirmed rubella
cases are the sum of laboratory-confirmed cases,
epidemiologically linked cases and clinically compatible
cases. However, when disease incidence is very low or a
country has achieved or nears rubella elimination, the
positive predictive value of the clinically compatible
case definition is low and most are likely not rubella.
Therefore, in eliminated and near-eliminated settings,
total cases are the sum of laboratory-confirmed and
epidemiologically linked cases, with the number of
clinically compatible cases provided separately. Imported
cases should be included in a country’s total case count,
unless the source country accepts the cases as part of
their case count. Imported cases should be included in
analysis but can be analysed separately.
SURVEILLANCE PERFORMANCE INDICATORS
Rubella surveillance should be evaluated routinely at
national and subnational/local levels, and is frequently
important in decision-making by national and regional
verification commissions. It is recommended that
countries review their national rubella surveillance
system annually as the country approaches, achieves
and sustains elimination. WHO has established criteria
against which rubella (and measles) surveillance should
WHO Vaccine-Preventable Diseases Surveillance Standards
Rubella
USING DATA FOR DECISION-MAKING
hh Confirm cases and outbreaks to take appropriate
action to prevent further transmission.
hh Determine risk factors for infection and
susceptibility gaps in population in order to target
vaccination efforts.
hh Review epidemiology, especially age distribution,
alongside CRS epidemiology to see if change in
vaccination strategy should be considered. Shifting
of rubella infection to older children and adults can
signal an impending CRS problem if the immunity
gap is not filled through enhanced vaccination
coverage.
hh Determine the extent of exposure among pregnant
women, as well as the risk and magnitude of possible
poor pregnancy outcomes in affected population.
hh Characterize transmission patterns and effectiveness
of methods to interrupt transmission (for example,
nosocomial).
hh Verify elimination and sustainability of elimination.
hh Because 20–50% of rubella cases are subclinical,
analysis of data from rubella surveillance should
be complemented with CRS surveillance data to
provide a more in-depth understanding of rubella
epidemiology in the country.
be evaluated (Table 2). Additionally, rubella surveillance
should be reviewed within the context of comprehensive
VPD surveillance reviews, which should be conducted at
least every five years.
Table 2 is a list of indicators against which the rubella
surveillance system can be evaluated in order to help
pinpoint problems and make improvements.
19
TABLE
Indicators of the quality of surveillance for rubella (and measles)
2
HOW TO CALCULATE
SURVEILLANCE
INDICATOR TARGET (NUMERATOR / COMMENTS
ATTRIBUTE
DENOMINATOR)

Percentage of ≥ 80% # of surveillance units At each level, reports should be

surveillance units in the country reporting received on or before the requested
TIMELINESS OF reporting to the by the deadline / # of date.
REPORTING national level on surveillance units in the
time, even in the country x 100
absence of cases

Percentage of 100% # of countries in the region At each level, reports should be

countries reporting reporting to WHO by the received on or before the requested
TIMELINESS
to their WHO deadline / # of countries date.
OF REPORTING
Regional Office on in the region x 100
(WHO REGION)
time, even in the
absence of cases

Percentage of all ≥ 80% # of suspected cases Note 1: An adequate investigation

suspected measles of measles or rubella includes collection of all the
and rubella cases for which an adequate following data elements from
that have had investigation was each suspected measles or rubella
an adequate initiated within 48 hours case: name or identifiers, place
investigation of notification / # of of residence, place of infection
initiated within 48 suspected measles and (at least to district level), age (or
TIMELINESS AND hours of notification rubella cases x 100 date of birth), sex, date of rash
COMPLETENESS onset, date of specimen collection,
OF measles-rubella vaccination
INVESTIGATION status, date of all measles-rubella
or measles-mumps-rubella
vaccination, date of notification,
date of investigation and travel
history.
Note 2: Some variables may not
be required for cases that are
confirmed by epidemiological
linkage (for example, date of
specimen collection).

Reporting rate of ≥ 2/ # suspected cases that

discarded non- 100,000 have been investigated
measles non- population and discarded as a
rubella cases at the per 12 non-measles and non-
national level months rubella case using (a)
laboratory testing in a
proficient laboratory
SENSITIVITY or (b) epidemiological
linkage to a laboratory-
confirmed outbreak of
another communicable
disease that is neither
measles nor rubella in a 12
month period / national
population x 100,000

20
Rubella
 Rubella

HOW TO CALCULATE
SURVEILLANCE
INDICATOR TARGET (NUMERATOR / COMMENTS
ATTRIBUTE
DENOMINATOR)

Percentage of ≥ 80% # confirmed cases in Unknown source should be kept

confirmed cases which the source can be to a minimum but will continue
for which source classified as endemic, to occur even with thorough field
SOURCE of transmission import, or importation- investigations. This target might not
CLASSIFICATION is classified as related / total number of be achievable in large outbreaks
endemic, imported confirmed cases x100
or importation-
related.

Percentage of ≥ 80% # of subnational units Note 1: If the administrative unit

subnational achieving ≥ 2 per has a population <100 000, the
administrative 100,000 population rate should be calculated by
units (at the discard rate / # of combining data over more than
province level or subnational units x 100 1 year for a given administrative
its administrative unit to achieve ≥100,000
equivalent) person-years of observation, or
reporting at neighboring administrative units
REPRESENTA- least 2 discarded can be combined for the purpose
TIVENESS non-measles of this calculation.
non-rubella cases
per 100,000 Note 2: Administrative units should
population per include all cases reported from
year their catchment area, including
import and importation-related
cases, and cases residing in
neighboring administrative units
but reported in this one.

Percentage of ≥ 80% # of suspected cases Note 1: Adequate specimens are:

suspected cases with an adequate a blood sample by venipuncture
with adequate specimen tested in in a sterile tube with a volume
specimens for a proficient lab / of at least 1 mL for older children
detecting acute # of suspected cases– and adults and 0.5 mL for infants
measles or rubella # of suspected cases and younger children; a dried
infection collected of measles or rubella blood sample, at least 3 fully filled
and tested in that are not tested circles on a filter-paper collection
a proficient by a laboratory and device; an oral fluid sample using
laboratory are (a) confirmed as a sponge collection device that
measles or rubella by is rubbed along the gums for
epidemiological linkage > 1 minute to ensure the device
SPECIMEN or (b) discarded as non- is thoroughly wet; a properly
COLLECTION measles and non-rubella collected upper respiratory tract
AND TESTING by epidemiological specimen for RT-PCR. Adequate
ADEQUACY linkage to another samples for antibody detection
laboratory-confirmed are those collected within 28 days
communicable disease after onset of rash, and for RT-
case x 100 PCR within 5 days of rash onset.
Note 2: A proficient laboratory is
one that is WHO accredited or
has established a recognized
quality assurance programme
(such as the International
Organization for Standards
(ISO) or Clinical Laboratory
Improvement Amendments (CLIA)
certified).

21
WHO Vaccine-Preventable Diseases Surveillance Standards
 HOW TO CALCULATE
SURVEILLANCE
INDICATOR TARGET (NUMERATOR / COMMENTS
ATTRIBUTE
DENOMINATOR)

Percentage of ≥ 80% # of outbreaks for which Where possible, samples should be

laboratory- adequate samples have collected from at least 5–10 cases
confirmed been submitted for viral early in a chain of transmission
outbreaks detection / # of outbreaks and every 2–3 months thereafter
with samples identified x 100 if transmission continues. For virus
VIRAL
adequate for detection, adequate samples are
DETECTION
detecting rubella those collected within 14 days of
virus collected rash onset.
and tested in
an accredited
laboratory

Percentage of ≥ 80% # of specimens received Indicator only applies to public

TIMELINESS specimens received within 5 days of collection laboratories.
OF SPECIMEN at the laboratory by laboratory / # of
TRANSPORT within 5 days of specimens x 100
collection

Percentage of IgM ≥ 80% # of IgM test results Indicator only applies to public
results reported reported within 4 days of laboratories.
TIMELINESS
to national public specimen receipt / # of
OF REPORTING
health authorities specimens received by lab
LABORATORY
by the laboratory x 100
RESULTS
within 4 days of
specimen receipt

CLINICAL CASE MANAGEMENT

Rubella is usually a mild, self-limiting disease that does should be placed on preventing exposure to pregnant
not require specific treatment. Patients with rubella women. Cases of CRS are managed differently, as
should have contact isolation precautions put in place for discussed in the CRS surveillance chapter.
seven days after they develop a rash. Particular emphasis

22
Rubella

CONTACT TRACING AND MANAGEMENT
Make every effort to conduct case investigations and
identify contacts for all suspected cases. Persons who
have been in contact with cases of rubella during their
infectious period (between 7 days before and 7 days after
the rash onset) should be located and interviewed to
determine their past exposure and vaccination status.
It is important to note that CRS cases themselves
can transmit rubella virus. Contacts of CRS cases are
different from contacts of acquired rubella as CRS cases
may shed rubella virus for up to 12 months from birth.
However, exposure for CRS cases is through contact
with the case (touching), while exposure from rubella
disease is through airborne transmission. Therefore, cases
should also be asked about exposure to potential CRS
cases.
Because of its infectious nature, contact tracing is
essential to determine both the source of infection for
the rubella case (endemic vs. imported/importation-
related), as well as identify those whom the case may
have subsequently infected. Any person who had contact
with the rubella case in the 7 days before rash onset
to 7 days after rash onset (or contact with a confirmed
CRS case) have been exposed and possibly infected,
and should be monitored by public health authorities
for 23 days from last contact with the confirmed case.
Contact for acquired rubella refers to sharing the same
WHO Vaccine-Preventable Diseases Surveillance Standards
Rubella
air space, usually an enclosed area, (for example, living in
the same household or being in the same room, school,
health facility waiting room, office or transport) for any
length of time with a case during the case’s infectious
period. Contact tracing is particularly important in
schools due to the intensity of exposure and the presence
of non-immune children. In healthcare settings, rubella
can also be amplified, with an elevated risk due the
presence of vulnerable, susceptible populations (such as
the very young, immunocompromised and patients with
underlying illnesses) as well as hospitalized CRS cases.
Pregnancy status should be determined for each female
contact so that appropriate follow-up can be done.
Pregnant contacts should be tested for rubella to rule
out infection and to confirm seroprotection. Pregnant
contacts who have evidence of infection should
be followed throughout the pregnancy. Currently,
there is limited evidence demonstrating that post-
exposure prophylaxis is efficacious. Immunoglobulin is
generally not recommended for routine post-exposure
prophylaxis of rubella, even when high titer anti-rubella
immunoglobulin is available. Vaccination can be given
in the first 48 hours after exposure to non-pregnant
contacts who have no documented protection against
rubella.
23
 SURVEILLANCE, INVESTIGATION AND RESPONSE
IN OUTBREAK SETTINGS
DEFINITION OF AN OUTBREAK
A single laboratory-confirmed case should trigger an
aggressive public health investigation and response in
an elimination setting. An outbreak is defined as two or
more laboratory-confirmed cases which are temporally
related (with dates of rash onset occurring 12–23 days
apart) and epidemiologically or virologically linked.
CHANGES TO SURVEILLANCE DURING AN
OUTBREAK
hh Enhance surveillance. Routine passive surveillance
should be enhanced during an outbreak (for example,
increasing awareness and messaging to clinicians
and laboratories). Active surveillance should be
established, including laboratory confirmation of
cases that are identified by regular visits and record
review at health facilities (both public and private,
and other settings). The investigation should also
include efforts to retrospectively find any cases that
preceded the first reported case to help determine
the time and circumstances of the beginning of the
outbreak and better assess its full extent. Establish
intensified surveillance in neighbouring villages,
districts and possibly provinces in response to
laboratory-confirmed cases or outbreaks to detect
and minimize the spread of the outbreak. If the
number of cases is large, line listing can be used for
collecting the key data elements.
hh Increased frequency of reporting. During an
outbreak, reporting should be at least weekly after
the initial report. If timely case-based reporting
during an outbreak is not feasible because of the
large number of cases, case-based data should still be
collected and entered into the database as soon as it
becomes feasible. Health workers should be alerted
about the rubella outbreak and given instructions on
where to report suspected cases. Weekly reporting,
including zero reporting in the absence of cases,
should continue for the duration of the outbreak and
for at least two incubation periods after the onset of
the last laboratory-confirmed or epidemiologically
linked case. Rubella outbreaks should be reported to
WHO through country and regional offices.
hh Changes to laboratory testing. During an outbreak,
laboratory confirmation should be sought for the
initial 5–10 cases in a given district (or equivalent
24
administrative unit). In addition to collecting
specimens for antibody detection, laboratory
confirmation should include obtaining specimens
for virus characterization in order to identify the
involved strain and its potential origin (endemic
versus imported). Once the outbreak is confirmed,
subsequent cases can be primarily confirmed based
on epidemiological linkage to a laboratory-confirmed
case. However, laboratory confirmation should be
sought for all suspected cases in pregnant women.
If suspected cases are reported outside the initially
affected geographic area and there is no clear
epidemiological linkage with the initial outbreak,
the first 5–10 suspected cases in these other areas
should also be tested to confirm the cause. If the
outbreak continues, another 5–10 suspected cases
should be tested every two months. Following
laboratory confirmation of initial rubella case(s),
emphasis should be given to epidemiological
investigation aimed at confirmation of new cases by
epidemiological linkage with the confirmed case.
Each outbreak should have a sample collected for
genotyping.
hh CRS surveillance. Establish or strengthen active
CRS surveillance in maternity hospitals, paediatric
hospitals, neonatal intensive care units and amongst
specialists who treat infants with cardiac, hearing
or eye problems. Prioritize hospitals located in the
area where the outbreak is occurring. Establish
a pregnancy registry to document all pregnancy
outcomes. These may include abortions (spontaneous
and therapeutic), fetal deaths, CRS cases and infants
with congenital rubella infection. As mortality of
children with CRS can be elevated for up to 2 years
of age, CRS surveillance should continue for one to
two years after the last rubella case.
Though very rare, concomitant outbreaks of measles
and rubella have been known to occur. It is important
in these settings to conduct good epidemiological
and laboratory investigations according to national
guidelines. Appropriate investigations will ensure
that appropriate response activities are implemented
including case management, vaccination response, and
infection control practices.
Rubella

PUBLIC HEALTH RESPONSE
Outbreak response immunization is indicated for
confirmed rubella outbreaks, specifically where
the vaccine has been introduced. The extent of the
vaccination response will depend on the epidemiological
picture. For sporadic cases and very small outbreaks of
fewer than 10 cases in geographically limited (same
village) or low-risk areas, it may be sufficient to do
selective immunization of contacts (excluding pregnant
women) in the immediate area of the outbreak (involved
and surrounding villages). Health staff without known
immunity to rubella should also be vaccinated, and
routine immunization services should be reinforced. For
SPECIAL CONSIDERATIONS FOR RUBELLA SURVEILLANCE
As rubella control progresses towards elimination, the
sensitivity and specificity of surveillance systems should
increase. If resources permit, periodic seroprevalence
surveys could be used to supplement the surveillance
data to identify immunity gaps in a population. These
WHO Vaccine-Preventable Diseases Surveillance Standards
Rubella
larger outbreaks or when the risk assessment indicates
there are large areas that are at risk, consider doing a
non-selective approach targeting larger areas, with the
target age group determined by disease epidemiology
and population immunity profiles.
Efforts should be made to minimize transmission in
healthcare settings, with particular emphasis on pregnant
women, by ensuring immunity of health workers
including public health staff, laboratory staff, medical
students and nursing students. Implement infection
control practices in healthcare settings (isolation of cases
up to seven days after rash onset.)
surveys could include collection of samples from women
attending antenatal clinics. Monitoring changes in age-
specific and sex-specific seroprevalence provides data for
identifying modifications that may need to be made to
the immunization strategy.
25
 REFERENCES

REFERENCES CITED
1. World Health Organization. Rubella vaccines: WHO position paper. Wkly Epidemol Rec. 2011;86(29):301–16
(http://www.who.int/wer/2011/wer8629.pdf ?ua=1).
2. World Health Organization. Roadmap to elimination-standard measles and rubella surveillance. Wkly Epidemiol Rec.
2017;92(9-10): 97–105 (http://apps.who.int/iris/bitstream/10665/254652/1/WER9209-10.pdf ?ua=1).
3. World Health Organization. Manual for the laboratory-based surveillance of measles, rubella, and congenital rubella syndrome,
3rd edition. Geneva: World Health Organization; 2018 (http://www.who.int/immunization/monitoring_surveillance/
burden/laboratory/manual/en/)
4. Vauloup-Fellous C, Grangeot-Keros L. Humoral immune response after primary rubella virus infection and after vaccination.
Clin Vaccine Immunol. 2017;14(5):644–647. doi.org/10.1128/CVI.00032-07
5. Mulders MN, Rota PA, Icenogle JP, Brown KE, Takeda M, Rey GJ, et al. Global measles and rubella laboratory network
support for elimination goals, 2010-2015. MMWR Morb Mortal Wkly Rep. 2017;65(17):438-442.
6. World Health Organization. Introducing rubella vaccine into national immunization programmes: a step-by-step guide.
Geneva: World Health Organization; 2015 (http://www.who.int/immunization/documents/who_ivb_15.07/en/).
7. World Health Organization. Framework for verifying elimination of measles and rubella. Wkly Epidemiol Rec.
2013;88(9):89-99 (http://www.who.int/wer/2013/wer8809.pdf).

ADDITIONAL REFERENCES
8. WHO Regional Office for Europe. Guidance on conducting serosurveys in support of measles and rubella elimination in the
WHO European Region. Copenhagen: WHO Regional Office for Europe; 2013 (http://www.euro.who.int/__data/assets/
pdf_file/0011/236648/Guidance-on-conducting-serosurveys-in-support-of-measles-and-rubella-elimination-in-the-
WHO-European-Region.pdf).
9. WHO Regional Office for Europe. Guidelines for measles and rubella outbreak investigation and response in the WHO
European Region. Copenhagen: WHO Regional Office for Europe; 2013 (http://www.euro.who.int/__data/assets/
pdf_file/0003/217164/OutbreakGuidelines-updated.pdf).
10. World Health Organization. Guidelines on the use of serosurveys in support of measles and rubella elimination. Geneva: World
Health Organization (draft); 2018.
11. Pan American Health Organization. Plan of action for documentation and verification of measles, rubella, and congenital
rubella syndrome elimination in the Region of the Americas. Washington, DC: Pan American Health Organization; 2011
(www.paho.org/hq/index.php?option=com_docman&task=doc_download).
12. WHO Regional Office for Europe. Surveillance guidelines for measles, rubella and congenital rubella syndrome in the WHO
European Region, update December 2012. Copenhagen: WHO Regional Office for Europe; 2012 (http://www.euro.who.int/
en/health-topics/communicable-diseases/measles-and-rubella/publications/2012/surveillance-guidelines-for-measles,-
rubella-and-congenital-rubella-syndrome-in-the-who-european-region,-update-december-2012).

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Rubella